title: Select dietary phytochemicals function as inhibitors of COX-1 but not COX-2.
abstract: Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are reported to suppress carcinogenesis by targeting COX-2. A major question was accordingly raised: why has the lifelong use of phytochemicals that likely inhibit COX-2 presumably not been associated with adverse cardiovascular side effects. To answer this question, we selected a library of dietary-derived phytochemicals and evaluated their potential cardiovascular toxicity in human umbilical vein endothelial cells. Our data indicated that the possibility of cardiovascular toxicity of these dietary phytochemicals was low. Further mechanistic studies revealed that the actions of these phytochemicals were similar to aspirin in that they mainly inhibited COX-1 rather than COX-2, especially at low doses.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Naomi
authors.initials: N
authors.lastname: Oi
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Lubet
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D064209:Phytochemicals / Q000494:pharmacology* / Q000633:toxicity; D013929:Thromboxane B2 / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D064209:Phytochemicals; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2